Professor
Public Health Research Institute Center
New Jersey Medical School - Rutgers, The State University of New Jersey
225 Warren Street
Newark, New Jersey 07103

Research Summary

Gilla Kaplan, Ph.D., Professor of Medicine in the Laboratory of Mycobacterial Immunity and Pathogenesis at the Public Health Research Institute Center of the University of Medicine and Dentistry of New Jersey. Dr. Kaplan’s expertise encompasses studies of human disease and animal models to better understand host immune responses and the role of cytokine production in the pathogenesis of microbial infections. For the past 30 years, Dr. Kaplan has been studying the role of macrophage activation in the host response, initially to tumors and later to mycobacterial infections. She and her colleagues have studied immune responses to intradermal administration of recombinant interferon gamma (rIFN-Gamma), interleukin 2 (rIL2) and macrophage colony stimulating factor (rGM-CSF) in persons with lepromatous leprosy; examined T cell responsiveness and suppression in leprosy; defined immune activation and gene expression in patients with tuberculosis (TB) following treatment with rIL-2; and characterized interactions between M. tuberculosis and HIV or M. leprae and HIV in co-infected patients. More recently, Dr. Kaplan and her group determined that the production of macrophage proinflammatory cytokines are differentially induced following infection with different clinical isolates of M. tuberculosis, leading to different extents of disease progression and clinical outcome. Dr. Kaplan and her team have shown that thalidomide treatment modifies TNF-Alpha and IL-12 production and can improve outcome in humans with lepromatous leprosy, TB or HIV infection, in animal models of inhalational TB (in mice) and TB meningitis (in rabbits), and in vitroin M.tuberculosis-infected human monocytes. Dr. Kaplan and her team have since developed two classes of novel, synthetic analogues of thalidomide that reduce TNF-Alpha production by 50,000 times more than the parent drug, thalidomide, and with fewer deleterious side effects. Co-treatment with these analogues, in combination with antibiotics, is significantly more efficient in reducing TNF-Alpha production and improving survival of rabbits with experimental TB meningitis than antibiotic treatment alone. The immunomodulatory drugs are being further tested as adjunctive therapy to antibiotic treatment in mice and rabbits with pulmonary TB to reduce tissue injury and improve response to treatment.

In addition to Dr. Kaplan's studies at the Public Health Research Institute, she has a number of off shore collaborative studies being conducted at the University of Cape Town, Cape Town, South Africa. The pathogenic process that occurs in the lung of TB patients is being analyzed and the effect of antiretroviral treatment of HIV infected individuals on TB disease and MTB transmission are being studied in collaboration with Dr. Linda-Gail Bekker Wood. In addition, immunologic correlates of BCG vaccination-induced protective immunity against TB disease in infants are being defined in collaboration with Dr (s) Willem Hanekom and Greg Hussey. Dr. Kaplan has recently begun a study to explore host and pathogen factors that contribute to the failure of treatment of MDR TB, ultimately leading to emergence of XDR TB strains in HIV-infected and non-HIV-infected patients in collaboration with Drs. Gerrit Coetzee, Clive Gray and Martin Grobusch of the National Health Laboratory Services and the University of the Witwatersrand in Johannesburg, South Africa. In addition, Dr. Kaplan is the PI of a Fogarty International Training Grant “Analysis of X/MDR TB strains: safety, diagnosis and pathogenesis. The grant will bring South African TB investigators to UMDNJ to train in TB molecular epidemiology, diagnostics and safe Biosafety Level 3 practices.